Brooke-Spiegler Syndrome Variant Segregation of Tumor Types with Mixed Differentiation in Two Generations

Abstract

Brooke-Spiegler syndrome (BSS) is an autosomal dominantly inherited disease characterized by the development of multiple trichoepitheliomas and cylindromas. Other lesions have been reported to occur in patients with BSS, including parotid basal cell adenomas, milia, organoid nevi, basal cell carcinomas, and spiradenomas. Spiradenomas and cylindromas have so many features in common that they have been regarded as polar extremes belonging to a spectrum of cutaneous adnexal neoplasms. We report on a 61-year-old woman with multiple spiradenomas on the scalp and periauricular areas and her 28-year-old daughter, with multiple facial trichoepitheliomas. Occasional features of pilar and ductal differentiation were found in tissue specimens of tumors from the mother and daughter, respectively. Co-existence of multiple spiradenomas and trichoepitheliomas and segregation of the predominant type of tumor in different members of a family with BSS have been reported occasionally, but never, to our knowledge, in combination. The presence of mixed differentiation in tumor specimens from both patients provides additional evidence in support of the folliculosebaceous apocrine unit (FSAU) hypothesis. Mutations in genes regulating proliferation and differentiation of putative stem cells of the FSAU would give rise to different combinations of adnexal skin tumors as well as to other neoplasms.

Multiple Familial Trichoepithelioma Caused by Mutations in the Cylindromatosis Tumor Suppressor Gene

“…Numerous reports of coexistence of both types of tumors in the same family and even in the same individual were published (27). There are too many well-documented kindreds in which subjects were affected with both types of tumors to suggest the possibility of a chance association of two separate autosomal mutations in each case (1,13,28,29). Moreover, syringomas that show differentiation toward sweat ducts may coexist with TEs (30).…”

Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing GLI-1

“…Furthermore, TEs and cylindromas often coexist in patients with the tumor predisposition syndrome hereditary multiple epithelioma (MIM 132700) (37,38). TE and BCC occur in the multiple familial TE syndrome (MIM 60͞606), and trichoblastoma and BCC often develop within a congenital malformation called sebaceous nevus, in which deletions in the PTCH1 gene region were recently reported (39)(40)(41).…”

Apocrine mixed tumor of the skin (“mixed tumor of the folliculosebaceous-apocrine complex”)

“…24 Both benign and malignant tumors, sporadic or associated with a genetic syndrome (such as BrookeSpiegler syndrome), have been shown to manifest combined follicular, sebaceous, and apocrine differentiation. [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] Apart from decapitation secretion, follicular differentiation was prevalent in this series, encountered in somewhat less than half the cases. This took the form of differentiation toward either or both the upper (infundibulum, isthmus) and the lower (stem, bulb) portions of the hair follicle.…”